Abstract Invasive cervical cancer (ICC) is a disease of disparities, with a higher risk among poor, rural, African American, Hispanic, and Native American women. ICC is preventable with adequate cytological screening, although there are several barriers to the access of screening and associated treatment for many high-risk women. The Behavioral Risk Factor Surveillance System (BRFSS) data show 13.3% of eligible women lacked screening for ICC in North Carolina within the last three years. We propose a pilot study to validate a mailed, at-home self-screening test for ICC. Among a sample of 200 women, we will explore psychological acceptance ofthe mailed self-administered screening test for ICC. Consenting rural women older than 30 years and lacking the proper screening schedule will recruited, asked to mail self-sampling kits, return mail cervico-vaginal specimens, and obtain HPV test results by telephone. HPV DNA positive, negative, and indeterminate women will be referred to the North Carolina Breast and Cervical Cancer Control Program to conduct a second self-sampling at the clinic, a physician-collected sample for HPV and cytological screening, and, if indicated, follow-up treatment. Consultations with participants will be conducted to help identify barriers to self-screening and to follow-up screening and treatment in order to increase the effectiveness of this proposed outreach program. This pilot study will assess HPV detection rates for HPV self-test collected at home, and subsequent in-clinic self-collected and practitioner-collected samples. Genital specimens will be tested for high-risk types of human papillomavirus (HPV) infection with Quigen HC-ll assay. Standardized testing will optimize our efforts to evaluate the validity of this mailed self-sampling model. If successful, a mailed at-home self-screening test can immediately impact the delivery of preventive screening for many at-risk women. Pilot data would justify a scale-up to other high-risk regional and national areas, assuming the successful return of self-collected samples, sample quality is confirmed, and assurance of in-clinic screening and appropriate follow-up.